Management of Hepatic Steatosis
All patients with hepatic steatosis require lifestyle modification as first-line therapy, with weight loss of 7-10% to improve inflammation and ≥10% to reverse fibrosis, combined with 150-300 minutes weekly of moderate-intensity exercise and a Mediterranean dietary pattern. 1, 2
Risk Stratification Determines Management Intensity
Begin by calculating the FIB-4 score and obtaining liver stiffness measurement (LSM) to stratify fibrosis risk, as this determines whether patients need hepatology referral and pharmacotherapy consideration. 1, 2
Low-risk patients (FIB-4 <1.3, LSM <8.0 kPa, or F0-F1 fibrosis) require only lifestyle interventions with annual non-invasive test monitoring. 2, 3
Intermediate-risk patients (FIB-4 1.3-2.67 or LSM 8.0-12.0 kPa) need closer monitoring and more aggressive lifestyle intervention. 1, 2
High-risk patients (FIB-4 >2.67, LSM >12.0 kPa, or ≥F2 fibrosis) require hepatology referral for multidisciplinary management and consideration of pharmacotherapy. 1, 2, 3
Lifestyle Interventions: The Foundation for All Patients
Weight Loss Targets
Prescribe specific weight loss goals based on desired outcomes, achieved gradually at <1 kg/week to avoid worsening liver injury. 2, 3
- 5% weight loss reduces liver fat 1, 4
- 7-10% weight loss improves steatohepatitis and inflammation 1, 4
- ≥10% weight loss reverses fibrosis 1, 4
The 2024 EASL-EASD-EASO guidelines provide the most recent evidence showing a dose-response relationship between weight loss magnitude and histological improvement. 1 Weight loss through structured programs is more effective than office-based counseling alone. 1, 3
Dietary Modifications
Implement a Mediterranean dietary pattern including vegetables, fruits, unsweetened high-fiber cereals, nuts, fish or white meat, and olive oil. 1, 2, 4
Eliminate completely: sugar-sweetened beverages 1, 4
Severely restrict: ultra-processed foods rich in sugars and saturated fat 1, 4
Coffee consumption is associated with improved liver outcomes in observational studies and can be encouraged. 1, 4
Exercise Prescription
Prescribe 150-300 minutes weekly of moderate-intensity exercise or 75-150 minutes weekly of vigorous-intensity exercise, tailored to individual ability. 1, 2, 4
Physical activity reduces steatosis and improves aminotransferases even without significant weight loss, making it beneficial for all patients including those at normal weight. 1, 4
Management of Cardiometabolic Comorbidities
Diabetes Management
Prioritize GLP-1 receptor agonists (semaglutide, liraglutide) as they improve both glycemic control and liver histology, with semaglutide achieving NASH resolution in 59% versus 17% with placebo. 1, 2, 4, 3
SGLT2 inhibitors (empagliflozin, dapagliflozin) are beneficial for patients with diabetes and hepatic steatosis. 1, 2
Pioglitazone increases odds of NASH resolution (OR 3.2) and fibrosis reversal (OR 3.1), though it causes modest weight gain (~2.7%) that can be mitigated with nutritional counseling or combination with GLP-1RAs/SGLT2 inhibitors. 3
Dyslipidemia Management
Prescribe statins for all patients with dyslipidemia, as they are safe in hepatic steatosis, have beneficial pleiotropic properties, and reduce HCC risk by 37% in meta-analyses. 1, 2, 4, 3
Hypertension Management
Manage hypertension according to standard guidelines, as cardiovascular disease is a leading cause of mortality in these patients. 1
Medications to Avoid
Stop or avoid medications that worsen steatosis: corticosteroids, amiodarone, methotrexate, tamoxifen, estrogens, tetracyclines, and valproic acid. 2, 3
Pharmacotherapy for Advanced Disease
Pharmacologic treatment is reserved only for patients with biopsy-proven NASH and significant fibrosis (≥F2) or high-risk features. 1, 3
Resmetirom (First-Line for Non-Cirrhotic NASH with ≥F2 Fibrosis)
Resmetirom is the preferred agent where approved locally for non-cirrhotic MASH with significant liver fibrosis (stage ≥F2), demonstrating histological efficacy on steatohepatitis and fibrosis in phase III trials with acceptable safety. 1, 4, 3
The 2024 EASL guidelines provide the most recent recommendation supporting resmetirom as first-line pharmacotherapy. 1
Vitamin E (Alternative for Non-Diabetic NASH)
Vitamin E 800 IU daily improved steatohepatitis in patients with biopsy-proven NASH without diabetes in large randomized trials, though safety concerns limit routine use. 1, 3
No Pharmacotherapy for Cirrhotic MASH
No MASH-targeted pharmacotherapy is currently recommended for cirrhotic-stage disease; management focuses on metabolic optimization, surveillance for complications, and transplant evaluation when decompensated. 1, 3
Bariatric Surgery Consideration
Consider bariatric surgery for patients with clinically significant fibrosis (≥F2) and obesity with comorbidities, as it achieves sustained weight loss and improves liver histology. 1, 4, 3
Bariatric surgery is currently underutilized despite strong evidence for efficacy in both obesity and NAFLD management. 1
Monitoring Strategy
Low-risk patients: Annual follow-up with repeated FIB-4 and/or LSM 2, 3
High-risk patients: Close hepatology follow-up with transient elastography monitoring, HCC surveillance every 6 months for advanced fibrosis (F3), and screening for varices if LSM ≥20 kPa or thrombocytopenia present. 4, 3
Common Pitfalls to Avoid
Do not prescribe nutraceuticals, as there is insufficient evidence of effectiveness or safety. 1
Do not delay hepatology referral for high-risk patients (FIB-4 >2.67, LSM >12.0 kPa), as nearly 10% of screened patients have clinically significant fibrosis requiring specialized management. 1, 2
Do not recommend rapid weight loss >1 kg/week, as this may worsen liver injury. 3
Do not withhold statins due to concerns about hepatotoxicity, as they are safe and beneficial in this population. 1, 2, 4, 3